“…However, there are drawbacks to using such carriers, including toxicity, inflammatory response, and reduced nucleotide release because of their high charge. High positive charge on the polymers can be modulated by adding functional groups (i.e., esters), which moderate the interaction and binding strength between the charged groups on the polymers and the encapsulated nucleotides. ,− New cationic polymers (i.e., PBAE (β-amino ester), Charge-altering releasable transporters (CARTs i.e α-amino ester), and PHTA) based on this approach are being investigated to deliver mRNA and short nucleotides for gene editing and vaccines with reduced toxicity and inflammatory response. − However, the in vivo long-term potential toxicity of the degraded products requires careful examination under biologically relevant conditions. The use of PBEA has been employed in the development of mRNA formulations intended for intranasal administration with the assistance of a nebulizer. , This utilization strongly indicates the enhanced stability of nanoparticles in withstanding the process of nebulization.…”